NZ247914A - Peptides having bradykinin antagonist activity, their preparation and compositions - Google Patents

Peptides having bradykinin antagonist activity, their preparation and compositions

Info

Publication number: NZ247914A
Authority: NZ; New Zealand
Prior art keywords: residue; radical; arg; formula; carbonyl
Prior art date: 1992-06-18

Application number

NZ247914A

Other languages

English (en)

Inventor

Jean-Luc Fauchere

Christophe Thurieau

Joseph Paladino

Nathalie Kurcharczyk

Emmanuel Canet

Original Assignee

Adir

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1992-06-18

Filing date

1993-06-17

Publication date

1994-12-22

1993-06-17 Application filed by Adir filed Critical Adir

1994-12-22 Publication of NZ247914A publication Critical patent/NZ247914A/en

Links

108090000765 processed proteins & peptides Proteins 0.000 title claims description 30
239000003152 bradykinin antagonist Substances 0.000 title claims description 10
UYRCOTSOPWOSJK-JXTBTVDRSA-N bradykinin antagonist Chemical compound C1C2=CC=CC=C2CC1[C@@H](NC(=O)C(CO)NC(=O)C(NC(=O)CNC(=O)[C@H]1N(C[C@H](O)C1)C(=O)C1N(CCC1)C(=O)C(CCCNC(N)=N)NC(=O)[C@@H](CCCNC(N)=N)NC(=N)CCCCCCC(=N)N[C@H](CCCNC(N)=N)C(=O)NC(CCCNC(N)=N)C(=O)N1C(CCC1)C(=O)N1[C@@H](C[C@@H](O)C1)C(=O)NCC(=O)NC(C1CC2=CC=CC=C2C1)C(=O)NC(CO)C(=O)N[C@H](C1CC2=CC=CC=C2C1)C(=O)N1C2CCCCC2CC1C(=O)NC(CCCNC(N)=N)C(O)=O)C1CC2=CC=CC=C2C1)C(=O)N1C2CCCCC2CC1C(=O)NC(CCCNC(=N)N)C(O)=O UYRCOTSOPWOSJK-JXTBTVDRSA-N 0.000 title claims description 5
230000000694 effects Effects 0.000 title description 6
102000004196 processed proteins & peptides Human genes 0.000 title description 6
238000002360 preparation method Methods 0.000 title description 5
239000000203 mixture Substances 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 33
-1 4-guanidinobenzoyl radical Chemical class 0.000 claims description 53
235000001014 amino acid Nutrition 0.000 claims description 30
150000001413 amino acids Chemical class 0.000 claims description 30
PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 claims description 19
230000015572 biosynthetic process Effects 0.000 claims description 14
FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 claims description 13
238000003786 synthesis reaction Methods 0.000 claims description 13
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 12
235000004279 alanine Nutrition 0.000 claims description 12
238000000034 method Methods 0.000 claims description 12
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 11
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 10
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
HGIPIEYZJPULIQ-UHFFFAOYSA-N 2-(methylazaniumyl)-2-phenylacetate Chemical compound CNC(C(O)=O)C1=CC=CC=C1 HGIPIEYZJPULIQ-UHFFFAOYSA-N 0.000 claims description 8
239000002253 acid Substances 0.000 claims description 7
125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 claims description 7
239000008194 pharmaceutical composition Substances 0.000 claims description 7
OMGHIGVFLOPEHJ-UHFFFAOYSA-N 2,5-dihydro-1h-pyrrol-1-ium-2-carboxylate Chemical compound OC(=O)C1NCC=C1 OMGHIGVFLOPEHJ-UHFFFAOYSA-N 0.000 claims description 6
108010077895 Sarcosine Proteins 0.000 claims description 6
125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims description 6
229940043230 sarcosine Drugs 0.000 claims description 6
238000010532 solid phase synthesis reaction Methods 0.000 claims description 6
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 5
125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
150000003254 radicals Chemical class 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 5
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 4
229910052799 carbon Inorganic materials 0.000 claims description 4
PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
229960002591 hydroxyproline Drugs 0.000 claims description 4
HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 claims description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
150000003839 salts Chemical class 0.000 claims description 4
FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 claims description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
239000004471 Glycine Substances 0.000 claims description 3
206010030113 Oedema Diseases 0.000 claims description 3
125000000217 alkyl group Chemical group 0.000 claims description 3
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 3
125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims description 3
125000003508 trans-4-hydroxy-L-proline group Chemical group 0.000 claims description 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
SCIFESDRCALIIM-VIFPVBQESA-N N-methyl-L-phenylalanine Chemical group C[NH2+][C@H](C([O-])=O)CC1=CC=CC=C1 SCIFESDRCALIIM-VIFPVBQESA-N 0.000 claims description 2
208000002193 Pain Diseases 0.000 claims description 2
102000007079 Peptide Fragments Human genes 0.000 claims description 2
108010033276 Peptide Fragments Proteins 0.000 claims description 2
230000000172 allergic effect Effects 0.000 claims description 2
125000000539 amino acid group Chemical group 0.000 claims description 2
125000003277 amino group Chemical group 0.000 claims description 2
150000005840 aryl radicals Chemical class 0.000 claims description 2
208000010668 atopic eczema Diseases 0.000 claims description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
208000035475 disorder Diseases 0.000 claims description 2
125000005843 halogen group Chemical group 0.000 claims description 2
TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 claims description 2
208000014674 injury Diseases 0.000 claims description 2
239000002674 ointment Substances 0.000 claims description 2
230000036407 pain Effects 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
230000035939 shock Effects 0.000 claims description 2
238000010561 standard procedure Methods 0.000 claims description 2
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 2
230000008733 trauma Effects 0.000 claims description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
230000005764 inhibitory process Effects 0.000 claims 4
241000700159 Rattus Species 0.000 claims 3
229920001525 carrageenan Polymers 0.000 claims 3
229940113118 carrageenan Drugs 0.000 claims 3
235000010418 carrageenan Nutrition 0.000 claims 3
239000000679 carrageenan Substances 0.000 claims 3
238000002347 injection Methods 0.000 claims 3
239000007924 injection Substances 0.000 claims 3
239000000243 solution Substances 0.000 claims 3
UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 claims 3
230000003110 anti-inflammatory effect Effects 0.000 claims 2
210000002683 foot Anatomy 0.000 claims 2
MHFXVTWXBSTWGL-PKPIPKONSA-N (2s)-2-(2h-pyran-2-ylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC1OC=CC=C1 MHFXVTWXBSTWGL-PKPIPKONSA-N 0.000 claims 1
IYKLZBIWFXPUCS-VIFPVBQESA-N (2s)-2-(naphthalen-1-ylamino)propanoic acid Chemical compound C1=CC=C2C(N[C@@H](C)C(O)=O)=CC=CC2=C1 IYKLZBIWFXPUCS-VIFPVBQESA-N 0.000 claims 1
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 1
239000002202 Polyethylene glycol Substances 0.000 claims 1
239000012153 distilled water Substances 0.000 claims 1
238000002474 experimental method Methods 0.000 claims 1
210000000548 hind-foot Anatomy 0.000 claims 1
238000012623 in vivo measurement Methods 0.000 claims 1
208000027866 inflammatory disease Diseases 0.000 claims 1
229920001223 polyethylene glycol Polymers 0.000 claims 1
238000010254 subcutaneous injection Methods 0.000 claims 1
239000007929 subcutaneous injection Substances 0.000 claims 1
238000005303 weighing Methods 0.000 claims 1
239000003814 drug Substances 0.000 abstract description 2
229940079593 drug Drugs 0.000 abstract 1
238000002483 medication Methods 0.000 abstract 1
229940024606 amino acid Drugs 0.000 description 25
239000011347 resin Substances 0.000 description 14
229920005989 resin Polymers 0.000 description 14
238000004458 analytical method Methods 0.000 description 13
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
238000001819 mass spectrum Methods 0.000 description 11
101800004538 Bradykinin Proteins 0.000 description 10
102400000967 Bradykinin Human genes 0.000 description 10
QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 10
QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 10
229960003767 alanine Drugs 0.000 description 9
238000005859 coupling reaction Methods 0.000 description 9
125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 8
230000008878 coupling Effects 0.000 description 8
238000010168 coupling process Methods 0.000 description 8
238000005406 washing Methods 0.000 description 8
210000004899 c-terminal region Anatomy 0.000 description 5
238000010511 deprotection reaction Methods 0.000 description 5
229960002429 proline Drugs 0.000 description 5
235000013930 proline Nutrition 0.000 description 5
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
WOUIMBGNEUWXQG-VKHMYHEASA-N Ser-Gly Chemical compound OC[C@H](N)C(=O)NCC(O)=O WOUIMBGNEUWXQG-VKHMYHEASA-N 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
230000004913 activation Effects 0.000 description 4
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
208000006673 asthma Diseases 0.000 description 4
239000007790 solid phase Substances 0.000 description 4
239000002904 solvent Substances 0.000 description 4
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
KDGARKCAKHBEDB-NKWVEPMBSA-N Ser-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CO)N)C(=O)O KDGARKCAKHBEDB-NKWVEPMBSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
206010003246 arthritis Diseases 0.000 description 3
238000006243 chemical reaction Methods 0.000 description 3
239000011521 glass Substances 0.000 description 3
230000004048 modification Effects 0.000 description 3
238000012986 modification Methods 0.000 description 3
238000010647 peptide synthesis reaction Methods 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
235000008729 phenylalanine Nutrition 0.000 description 3
238000012360 testing method Methods 0.000 description 3
QTWZCODKTSUZJN-LJAQVGFWSA-N (2s)-5-[[amino-[(2,2,5,7,8-pentamethyl-3,4-dihydrochromen-6-yl)sulfonylamino]methylidene]amino]-2-(9h-fluoren-9-ylmethoxycarbonylamino)pentanoic acid Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)N[C@H](C(O)=O)CCCN=C(N)NS(=O)(=O)C(C(C)=C1C)=C(C)C2=C1OC(C)(C)CC2 QTWZCODKTSUZJN-LJAQVGFWSA-N 0.000 description 2
MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 2
WTOFYLAWDLQMBZ-UHFFFAOYSA-N 2-azaniumyl-3-thiophen-2-ylpropanoate Chemical compound OC(=O)C(N)CC1=CC=CS1 WTOFYLAWDLQMBZ-UHFFFAOYSA-N 0.000 description 2
239000004475 Arginine Substances 0.000 description 2
COLNVLDHVKWLRT-MRVPVSSYSA-N D-phenylalanine Chemical compound OC(=O)[C@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-MRVPVSSYSA-N 0.000 description 2
229930182832 D-phenylalanine Natural products 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
206010020751 Hypersensitivity Diseases 0.000 description 2
208000001953 Hypotension Diseases 0.000 description 2
206010061218 Inflammation Diseases 0.000 description 2
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
206010039085 Rhinitis allergic Diseases 0.000 description 2
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
239000004473 Threonine Substances 0.000 description 2
201000010105 allergic rhinitis Diseases 0.000 description 2
150000001408 amides Chemical group 0.000 description 2
229960003121 arginine Drugs 0.000 description 2
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
235000009697 arginine Nutrition 0.000 description 2
RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 2
238000001914 filtration Methods 0.000 description 2
229960002449 glycine Drugs 0.000 description 2
108010079596 glycyl-4-hydroxyproline Proteins 0.000 description 2
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230000004054 inflammatory process Effects 0.000 description 2
210000004731 jugular vein Anatomy 0.000 description 2
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
CMWYAOXYQATXSI-UHFFFAOYSA-N n,n-dimethylformamide;piperidine Chemical compound CN(C)C=O.C1CCNCC1 CMWYAOXYQATXSI-UHFFFAOYSA-N 0.000 description 2
229960005190 phenylalanine Drugs 0.000 description 2
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210000002460 smooth muscle Anatomy 0.000 description 2
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LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical class CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
REITVGIIZHFVGU-IBGZPJMESA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-[(2-methylpropan-2-yl)oxy]propanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](COC(C)(C)C)C(O)=O)C3=CC=CC=C3C2=C1 REITVGIIZHFVGU-IBGZPJMESA-N 0.000 description 1
BVAUMRCGVHUWOZ-ZETCQYMHSA-N (2s)-2-(cyclohexylazaniumyl)propanoate Chemical compound OC(=O)[C@H](C)NC1CCCCC1 BVAUMRCGVHUWOZ-ZETCQYMHSA-N 0.000 description 1
SAAQPSNNIOGFSQ-LURJTMIESA-N (2s)-2-(pyridin-4-ylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC1=CC=NC=C1 SAAQPSNNIOGFSQ-LURJTMIESA-N 0.000 description 1
WAMWSIDTKSNDCU-ZETCQYMHSA-N (2s)-2-azaniumyl-2-cyclohexylacetate Chemical compound OC(=O)[C@@H](N)C1CCCCC1 WAMWSIDTKSNDCU-ZETCQYMHSA-N 0.000 description 1
JBZXLQHJZHITMW-RXYZOABWSA-N (2s,3as,7as)-1-(9h-fluoren-9-ylmethoxycarbonyl)-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)N1[C@H]2CCCC[C@H]2C[C@H]1C(=O)O JBZXLQHJZHITMW-RXYZOABWSA-N 0.000 description 1
WPBXBYOKQUEIDW-VFNWGFHPSA-N (2s,4r)-1-(9h-fluoren-9-ylmethoxycarbonyl)-4-[(2-methylpropan-2-yl)oxy]pyrrolidine-2-carboxylic acid Chemical compound C1[C@H](OC(C)(C)C)C[C@@H](C(O)=O)N1C(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 WPBXBYOKQUEIDW-VFNWGFHPSA-N 0.000 description 1
GQDGUWUZRNZICA-MRVPVSSYSA-N (3R)-1,2,3,4-tetrahydro-2,6-naphthyridine-3-carboxylic acid Chemical group C1=CN=CC=2C[C@@H](NCC1=2)C(=O)O GQDGUWUZRNZICA-MRVPVSSYSA-N 0.000 description 1
GGAQJTYXDNHAPI-MRVPVSSYSA-N (3R)-1,2,3,4-tetrahydro-2,7-naphthyridine-3-carboxylic acid Chemical group C1=NC=CC=2C[C@@H](NCC1=2)C(=O)O GGAQJTYXDNHAPI-MRVPVSSYSA-N 0.000 description 1
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NZ247914A 1992-06-18 1993-06-17 Peptides having bradykinin antagonist activity, their preparation and compositions NZ247914A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
FR9207378A FR2692581B1 (fr)	1992-06-18	1992-06-18	Nouveaux dérivés peptidiques à activité antagoniste de la bradykinine, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent.

Publications (1)

Publication Number	Publication Date
NZ247914A true NZ247914A (en)	1994-12-22

Family

ID=9430857

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NZ247914A NZ247914A (en)	1992-06-18	1993-06-17	Peptides having bradykinin antagonist activity, their preparation and compositions

Country Status (12)

Country	Link
EP (1)	EP0578521B1 (de)
JP (1)	JP2589937B2 (de)
AT (1)	ATE141615T1 (de)
AU (1)	AU660809B2 (de)
CA (1)	CA2098655A1 (de)
DE (1)	DE69304155T2 (de)
DK (1)	DK0578521T3 (de)
ES (1)	ES2091570T3 (de)
FR (1)	FR2692581B1 (de)
GR (1)	GR3021472T3 (de)
NZ (1)	NZ247914A (de)
ZA (1)	ZA934389B (de)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ES2218554T3 (es) *	1994-10-27	2004-11-16	Fujisawa Pharmaceutical Co., Ltd.	Piridopirimidonas, quinolinas y n-heterociclos condensados que son antagonistas de bradiquinina.
FR2739553B1 (fr) *	1995-10-06	1998-01-02	Oreal	Utilisation d'antagonistes de la bradykinine pour stimuler ou induire la pousse des cheveux et/ou stopper leur chute
DE19612067A1 (de) *	1996-03-27	1997-10-02	Hoechst Ag	Verwendung von Bradykinin-Antagonisten zur Herstellung von Arzneimitteln zur Behandlung von chronisch fibrogenetischen Lebererkrankungen und akuten Lebererkrankungen
DE19642289A1 (de)	1996-10-14	1998-04-16	Hoechst Ag	Verwendung von Bradykinin-Antagonisten zur Herstellung von Arzneimitteln zur Behandlung und Prävention der Alzheimer'schen Krankheit
US7105172B1 (en)	1999-11-18	2006-09-12	Bolla John D	Treatment of rosacea
WO2016151753A1 (ja) *	2015-03-24	2016-09-29	日立金属株式会社	複合ケーブル、複合ハーネス、及び車両

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IE63490B1 (en) *	1988-11-24	1995-05-03	Hoechst Ag	Peptides having bradykinin antagonist action
MX9100717A (es) *	1990-08-24	1992-04-01	Syntex Inc	Antagonistas de la bradiquinina
FR2686343B1 (fr) *	1992-01-17	1994-03-11	Adir Cie	Nouveaux derives pseudopeptidiques a activite antagoniste de la bradykinine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent.

1992
- 1992-06-18 FR FR9207378A patent/FR2692581B1/fr not_active Expired - Fee Related
1993
- 1993-06-17 EP EP93401552A patent/EP0578521B1/de not_active Expired - Lifetime
- 1993-06-17 CA CA002098655A patent/CA2098655A1/fr not_active Abandoned
- 1993-06-17 AU AU41287/93A patent/AU660809B2/en not_active Ceased
- 1993-06-17 DK DK93401552.0T patent/DK0578521T3/da active
- 1993-06-17 JP JP5145942A patent/JP2589937B2/ja not_active Expired - Lifetime
- 1993-06-17 NZ NZ247914A patent/NZ247914A/en unknown
- 1993-06-17 DE DE69304155T patent/DE69304155T2/de not_active Expired - Fee Related
- 1993-06-17 AT AT93401552T patent/ATE141615T1/de not_active IP Right Cessation
- 1993-06-17 ES ES93401552T patent/ES2091570T3/es not_active Expired - Lifetime
- 1993-06-18 ZA ZA934389A patent/ZA934389B/xx unknown
1996
- 1996-10-24 GR GR960402827T patent/GR3021472T3/el unknown

Also Published As

Publication number	Publication date
CA2098655A1 (fr)	1993-12-19
EP0578521A1 (de)	1994-01-12
DK0578521T3 (da)	1996-12-09
DE69304155D1 (de)	1996-09-26
JP2589937B2 (ja)	1997-03-12
FR2692581A1 (fr)	1993-12-24
EP0578521B1 (de)	1996-08-21
DE69304155T2 (de)	1997-03-20
ES2091570T3 (es)	1996-11-01
ATE141615T1 (de)	1996-09-15
FR2692581B1 (fr)	1994-08-19
AU660809B2 (en)	1995-07-06
GR3021472T3 (en)	1997-01-31
JPH0687891A (ja)	1994-03-29
ZA934389B (en)	1994-01-17
AU4128793A (en)	1993-12-23

Publication	Publication Date	Title
KR100304201B1 (ko)	2001-11-30	환상의부착저해제
CA2075878C (en)	2002-12-24	Cyclic peptides and use thereof
SK13082001A3 (sk)	2002-03-05	Cyklický peptidový analóg a jeho výroba
JPH0610184B2 (ja)	1994-02-09	非天然アミノ酸
KR0173976B1 (ko)	1999-02-01	브라디키닌에 대하여 길항작용을 하는 펩타이드
EP0017746B1 (de)	1983-01-26	Peptide mit Somatostatin-Wirkung, sie enthaltende Zusammensetzungen und Verfahren zur Herstellung der Peptide
EP2161037A2 (de)	2010-03-10	Camptothecin-Somatostatin Konjugaten
EP0363589A2 (de)	1990-04-18	Somatostatin-Analoge
US4320118A (en)	1982-03-16	Deca-, undeca-, dodeca- and tridecapeptides with thymic activity
JPH0153268B2 (de)	1989-11-13
EP0269299A2 (de)	1988-06-01	Atriale Peptide
AU660809B2 (en)	1995-07-06	New peptide compounds having bradykinin-antagonist activity, process for their preparation and the pharmaceutical compositions which contain them
NO854645L (no)	1986-05-22	Fremgangsmaate for fremstilling av basiske cykliske peptider.
JP2949129B2 (ja)	1999-09-13	胃腸運動刺激活性を有するモチリン類似ポリペプチド
US5597803A (en)	1997-01-28	Bradykinin peptides with modifications at the N terminus
WO1989010935A1 (en)	1989-11-16	Atrial peptide derivatives
US5409899A (en)	1995-04-25	Pseudopeptide compounds having anti-inflammatory activity
EP0018182B1 (de)	1982-10-20	Peptide mit Thymopoietin-ähnlicher Wirksamkeit, sie enthaltende Arzneipräparate und Verfahren zu ihrer Herstellung
CA1246059A (en)	1988-12-06	Polypeptide-diesters, their production and use
EP0002262B1 (de)	1983-09-14	Mit Somatostatin verwandte Verbindungen und Verfahren zu deren Herstellung
NZ233795A (en)	1992-07-28	Derivatives of atrial natriuretic peptide (anp)
JPS61137898A (ja)	1986-06-25	Ｖ↓１‐バソプレシン拮抗剤
CZ286170B6 (cs)	2000-02-16	Cyklopeptidy
JPS62209096A (ja)	1987-09-14	バソプレシン化合物
EP0346068A2 (de)	1989-12-13	D-Cys6-Vasopressin-Antagonisten